Anxiety disorders are now a major mental illness worldwide. In an attempt to determine the neurobiological basis of fear and anxiety, researchers have demonstrated in animal studies that there is an innate brain system that detects and responds to threats to health. This system is often referred to as the “fear system” and is thought to underlie the conscious feeling of fear and the behavioral and physiological responses that accompany this feeling. However, research based on the “fear system” hypothesis has not led to the discovery of successful clinical treatments in humans as had been hoped.

The Amygdala Is Not the Source of Fear

The experience of danger leads to almost automatic bodily responses. Mammals, including humans, freeze when faced with sudden danger, such as an attacker. Dr. LeDoux is a leader in discovering how external threats initiate this defensive response. Utilizing a variety of techniques and techniques—including behavioral methods such as Pavlovian conditioning, as well as restraint tracing, electron microscopy, cell physiology, pharmacology, and molecular manipulation—his work implicates the amygdala in processing threat and control.

The amygdala is a paired structure, one on each side, located beneath the neocortex, the outer layer of the brain that underlies thinking, planning, and even consciousness. The amygdala is traditionally considered the center of the brain’s “fear” circuitry, helping to ensure survival in the face of harmful threats. This brain region is so important that animals or humans with damage to the amygdala are unable to mount behavioral and physiological responses to threats.

Fear Consciousness

Dr. Ledoux believes that although the amygdala detects and responds to danger, it is not a “fear center” as is often thought because it is not itself responsible for conscious feelings of fear. His conclusion is supported by a study showing that while damage to the amygdala in humans eliminates responses to threats, it does not prevent people from feeling fear. LeDoux believes that the subjective experience of fear and other emotions (such as anxiety) is processed by higher-order brain circuits primarily involving the prefrontal cortex. These circuits form the basis of cognitive processes such as attention, working memory, and decision-making. Neural connections in these networks allow you to understand the threat based on memories, including memories of what emotions are (emotion schemas) and who you are (ego schemas), to label this state with language, and to consciously experience fear, feeling like your happiness is at risk.

From Existential Threats to Modern Concerns

Although survival requires innate and immediate responses to threats, modern society introduces new challenges that require active monitoring of potential harm. We are less likely to fall prey to predators every day and instead worry about economic security, job satisfaction, politics, and the meaning of life. Worry can manifest as anxiety disorders or obsessive behaviors toward selected objects or other people. Symptoms of panic disorder include excessive anticipation of disaster, but there are also physical signals such as shaking, sweating, and involuntary muscle tension. Consistent with Dr. LeDoux’s conclusion, it is this complex interplay between conscious and unconscious factors that makes anxiety disorders difficult to treat.

Why Treatments Aren’t So Successful

Progress in providing effective treatments and clinical options for people with anxiety disorders has been slow. Overreliance on animal studies has led to an underrecognition of the contribution of cortical networks to the biological basis of fear and anxiety – which is important when seeking new treatments. Although mice and humans may share the same underlying biology that facilitates rapid behavioral and physiological responses to danger, the neural circuitry underlying the conscious experience of fear in humans is poorly developed in rodents. Ledoux argued that emotions like fear are not behavioral and physiological responses that can be studied equally in humans and other animals, but are conscious experiences that can only be understood directly through introspection. This does not mean that animal research has no place. Drugs developed through animal behavioral research are necessarily more likely to affect pathological behaviors such as avoidance rather than pathological feelings of fear or anxiety.

A Dual-Systems Framework for Better Treatment Options

In a recent article, Dr. LeDoux and psychiatrist Daniel Pine suggest a conceptual reframing of current approaches to fear and anxiety using what they call a dual-systems framework. This revolutionary approach advocates distinguishing between subjective feelings and defensive behaviors. If a drug treats the physical symptoms of a panic attack, it doesn’t necessarily mean the person will feel less anxious. Symptoms such as sweating or heavy breathing may decrease, but the subjective experience may not change (or not change enough to make the patient feel better). In fact, clinical studies have repeatedly shown that anxiety medications, while helpful in some cases, don’t meet many patients’ expectations.

Combined and Customized Treatments

Drug treatment combined with cognitive therapy has shown greater improvement rates in some studies, possibly because drugs target the subcortical behavioral control system more, while cognitive therapy affects the cortical subjective experience system to a greater extent: Both must be treated. More experimental treatment options, including new biological or behavioral approaches, might target certain circuits individually to observe changes in one circuit and then proceed to treat another circuit. Additionally, neuroimaging methods may provide more advanced insights and actionable biomarkers in the future to advance the development of more precise treatment options. However, individual differences between patients remain one of the biggest obstacles to finding optimal solutions. Dr. LeDoux’s dual systems approach makes the case for a brain-informed treatment plan, in which treatments target symptoms that are products of different systems in hopes of better meeting the patient’s individual needs.